Oral compositions

ABSTRACT

A chewable composition for teeth-whitening comprising a first region and a second region separated by a barrier layer; the first region comprising carbamide peroxide having water content of about 2% or less, a wetting agent (e.g., glycerin), an anhydrous chewing gum base having water content of about 1% or less, an anhydrous fruit acid, and one or more gum additives; and the second region comprising a chewable composition comprising a gum base, a source of bicarbonate ion, and one or more gum additives. A kit comprising separate chewable compositions corresponding to the first and second regions, and methods for whitening teeth using the chewable composition are also provided.

FIELD

The present disclosure relates to novel oral care compositions andmethods of their use for cosmetic as well as chemotherapeutic purposes.More particularly, the disclosure relates to chewing gums forteeth-whitening.

BACKGROUND OF THE INVENTION

Teeth whiteners, also known as teeth bleaching agents, are in widespreaduse as a cosmetic means to enhance appearance and to contribute tobetter oral health and hygiene in general. Among teeth whiteningformulations, those containing oxidizing agents as active ingredientsare preferred because of their fast action and superior efficacy. Themost frequently employed oxidizer in teeth whitening compositions is aperoxide, either in free form as hydrogen peroxide, or as a non-covalentadduct with urea. Such an adduct is known as carbamide peroxide (or ureahydrogen peroxide). It has been well established that the higher theconcentration of peroxide, the faster the whitening effect is achieved.However, it is important to note that the higher the concentration ofperoxide, the greater the risk of gum and teeth root sensitivity, whichhas proven a significant problem for at least 10-15% of the population.Also, the higher the concentration of peroxide in the teeth-whitener,the higher the probability that the teeth-whitener will not be stable orhave suitable shelf life for commercialization.

In general, stability is in direct conflict with the purpose of theperoxide-based teeth whitening compositions, which is to achieve thebest possible whitening in a reasonable length of time of contact withthe tooth surface. To accomplish this, the peroxide moiety must beshort-lived (on the order of seconds) in the mouth, decomposing into an“active oxygen moiety” which is the ultimate effective teeth whiteningagent. The requirement for quick decomposition in the mouth to generatethe active oxygen moiety is in conflict with the need for long shelflife necessary for commercialization. The greater the stabilization, theslower the reactivity of the peroxide moiety, and the less effective theteeth-whitening action.

To improve on the rate of teeth-bleaching action of shelf-stableperoxide-based teeth-whiteners in the mouth, “activators” have beendeveloped. For example, activation by use of UV light has been taught byU.S. Pat. Nos. 5,713,738 and 5,645,428 to Yarborough. For hydrogenperoxide, which is known to decompose in alkaline media, basic compoundsand alkaline systems have also been disclosed as activators for hydrogenperoxide teeth-whiteners. For example, Allred, U.S. Pat. No. 6,746,664B2 describes a variety of alkaline activation systems for whiteningteeth. These alkaline agents are provided as a separate component that,when admixed with the hydrogen peroxide composition, reduces the timefor hydrogen peroxide to react. However, it is known professionally thatmany of these teeth-whitening gels and gels with alkaline activatorscause extreme sensitivity to the hard and soft tissue. Hydrogen peroxideis known to decompose in the presence of alkaline media. It is believedthat the more rapid bleaching of the teeth is a direct consequence ofthe action of “activator.” These alkaline agents typically include pHmodifiers, including metal carbonates, metal bicarbonates, phosphates,amines and others. It is important to note, that even though the pH iscontrolled at a safe level by the addition of an alkaline based“activator,” effectiveness of these activators in enhancingteeth-whitening reactivity of a hydrogen peroxide teeth-whitener systemis questionable since they have not been shown to be better than thecorresponding non-activated hydrogen peroxide teeth-whiteningcompositions (typically gels or pastes). Further, it should be notedthat no significant difference in activation or teeth-whitening benefitshas been reported for any metal carbonates or metal bicarbonates.Typically, in the prior art, a metal carbonate salt such as calciumcarbonate, is the preferred activating and pH buffering agent.

Traditional teeth-whitening compositions and devices can be classifiedin three groups based on the method of delivering the material to toothsurfaces. The first is whitening toothpastes in which bleaching agentsare typically incorporated as an additional component in the toothpasteformulations. These have not proven to be effective. The second groupcontains formulations intended specifically for whitening teeth, usuallyin gel form, which are typically delivered to the tooth surface byfabricated trays. Such material may be administered under the control ofa dental professional or designed for in-home use. These treatments canbe considered as the most effective among commercial treatments. Thethird group includes products designed to be used without the need of adental professional and can be referred to as “out-of-office” products.Examples include strips, sprays, teeth-wipes, pens, and chewing gumproducts. A subset of these out-of-office products includes convenienceas a main factor distinguishing the products. A chewing gum that servesto whiten the teeth is the most convenient form of a teeth-whitenersince it is easy to carry and travel with, discrete when it is used, andnon-intrusive for typical social activities.

Chewing gum whitening products offer an attractive alternative to morecumbersome and time intensive whitening systems because they aresubstantially more user friendly. People find chewing gum pleasurableand are willing to chew gum for much longer periods of time than theytypically wear trays or brush their teeth. Such a method of deliveryoffers whitening action without sacrifice of time or comfort.

In general, the common shortcomings of existing “out-of-office”peroxide-based teeth whitening devices, especially those based onhydrogen or carbamide peroxides, are the inherent instability and lackof teeth-whitening efficacy. The efficacy of known teeth-whiteningdevices, especially that of chewing gum compositions, deteriorates overtime, particularly when exposed to elevated temperatures and humidconditions.

Anhydrous carbamide peroxide is the most effective form of hydrogenperoxide that can be used in chewing gums since it is available in a thyform and is relatively stable in an essentially the anhydrous state.However, carbamide peroxide is particularly prone to accelerateddecomposition when in contact with water, with other ingredients commonto chewing gums such as metal ions from the various particulate matterpresent in the gum compositions, and with alkaline agents (e.g., calciumcarbonate) or other alkaline materials. Gloulet, U.S. Pat. No.5,500,207, teaches a chewing gum comprising carbamide peroxide as theactive teeth-whitening agent and is a prime example of one suchcomposition not suitable for commercialization due to the inherent shortshelf-life of these unstabilized carbamide peroxide. Carbamide peroxideis prone to hydration and once carbamide peroxide becomes hydrated, evento a small degree, it begins to decompose. Since hydration happensreadily, unstabilized carbamide peroxide gum compositions do not havethe shelf-life required for commercial products.

With regard to additives that stabilize carbamide peroxides, the currentunderstanding is that the use of stabilizing additives iscounterproductive because incorporation of such materials negativelyaffects the product's whitening efficacy. See, for example, Howard, U.S.Pat. No. 5,824,291, which discloses the use of divalent metal peroxidesand an alkaline gum base. These compositions have not proven effectivefor commercialization, most likely due to the lack of whiteningactivity, and also to short shelf life, which is most likely a directconsequence of the absence of a barrier between the alkaline substance(activator) and the peroxide moiety (divalent metal peroxide). In starkcontrast to Howard, Orlaowski, et.al. U.S. Pat. No. 6,696,043 teaches adivalent metal peroxide that is activated by fruit acid, but also wherethere is a barrier between the fruit acid and metal peroxide to keep themetal peroxide from having contact with the fruit acid activator. Foractivity, the fruit acid and metal peroxide must first make contact,then react together in an aqueous environment (saliva). Here, theperoxide is stabilized by a non-reactive metal carbonate, and even upon“activation” by the fruit acid, does not provide for an effective dosageof “active peroxide” to realize any appreciable teeth whitening.

Microencapsulation has also been employed to aid in the stabilization ofcarbamide peroxide in chewing gum compositions. Microencapsulation istypically used as a means to protect actives in vitamin and foodcompositions. In microencapsulation, a barrier material is used to keepwater and other materials from contacting the active ingredient andcausing unwanted decomposition reactions. For teeth-whiteners, theactive agent is typically carbamide peroxide. Gebreselassie(WO/2012/145611) and WO 2006/086061 teach improved stability ofcarbamide peroxide in chewing gum compositions by use ofmicroencapusation technologies. However, these technologies have not yetresulted in an effective teeth-whitening chewing gum.

The requirement of anhydrous conditions places an additional limitationon chewing gum compositions taught in the prior art. Since prior artperoxide containing teeth-whitening chewing gum compositions requirerigorously anhydrous compositions, they cannot be “extruded,” andrequire compression using a conventional tablet press to produce thechewing gum composition. These tableted chewing gum compositions sufferfrom poor mouth feel, since they typically do not have the pleasantcharacteristics of the well-accepted commercial chewing gum products,which are made by extrusion. All commercial chewing gum products intoday's marketplace, having blended composition and different shapes,including sticks, coated compositions, etc., are extruded. Extruded gumsare more desirable, as they have a much better “mouth-feel” and, thus,are the most popular chewing gums in the marketplace. It is the watercontent of the “extrudable” chewing gum compositions that gives rise toperoxide containing chewing gum's unsuitability for extrusion. Thisinstability is most likely due to the increased amount of glycerin (or“polyol lubricant”) present in the extruded gum formulations. Glycerin(and propylene glycol) is extremely hygroscopic and always contains somewater. As a result, such “extrudable” teeth-whitening chewing gumscomprising a peroxide source (carbamide peroxide, metal peroxide, etc.)are not stable, and therefore not commercially viable. This instabilityis due to decomposition of the carbamide peroxide upon contact withwater internal to the chewing gum composition. As a result, extrudablechewing gum compositions for teeth-whitening comprising a peroxidesource, and specifically carbamide peroxide, have not been realizedcommercially.

It is important to also note that the teeth-whitening chewing gumcompositions of prior art have not been shown to have any appreciableteeth-whitening efficacy. At best, they may be used for maintenance ofteeth whiteness or for breath-freshening, not as a primaryteeth-whitening device.

Further, abrasives and surfactants, claimed to have teeth-whiteningactivity, have been described as a substitute for peroxide in chewinggums. For example, Lawlor, WO 02/092027 and Luo, U.S. Pat. No.:6,696,044 each teach a teeth-whitening gum that uses a surfactant as theactive whitening agent. Robinson, U.S. Pat. No.: 6,416,744, teaches achewing gum with silica as an abrasive and the active agent forteeth-whitening. However, none of Lawlor, Luo and Robinson provides acomposition with any noticeable teeth-whitening activity. Sodiumbicarbonate also has been used as a whitening agent. For example, RakshaK Ballal et al. (Int. J. Clin. Pediatr. Dent. 2016;9(1):35-38) teaches agum made with sodium bicarbonate to control pH of the saliva.Teeth-whitening activity of sodium bicarbonate chewing gums is nominalat best since they do not function to chemically remove stains. Thereare no reports of any significant teeth whitening achieved using achewing gum comprising chiefly sodium bicarbonate as the activeteeth-whitening agent.

Of importance chemotherapeutically, Dr. Keyes (National Institutes ofHealth) discovered that the use of hydrogen peroxide and baking soda(sodium bicarbonate) is useful as preventative and remedial treatmentfor periodontal diseases. Others using his technique also noted ateeth-whitening effect. In fact, the whitening effects of hydrogenperoxide aqueous solutions were first reported by the periodontalcommunity in the 1970s. The use of hydrogen peroxide and baking soda asan efficacious combination for teeth-whitening, however, has never beenreported, even though the use has been theorized, taught, and practicedas remedy and for the prevention of gingival diseases. Further, based onthe available knowledge, sodium bicarbonate is not regarded to be asgood an activator as sodium carbonate or potassium carbonate, which arestronger alkaline buffering agents.

One major drawback of the use of oral compositions having hydrogenperoxide in combination with alkaline activating agents, andspecifically with carbonate and bicarbonate salts such as baking soda(sodium bicarbonate), is the inherent incompatibility of these agentswith hydrogen peroxide. Hydrogen peroxide decomposes quickly in thepresence of bases. Sodium bicarbonate is such a base. Prior art teachingrelating to a hydrogen peroxide source and alkaline activator do notrequire a barrier between the activator (e.g., bicarbonate ion) andperoxide and thus, the combination is unstable. Also, the strengths ofthe two actives in gum compositions taught in the prior art are too lowfor achieving any appreciable teeth whitening in one treatment, and mostlikely even in multiple treatments.

For a commercial product, it is preferable that the two actives(hydrogen peroxide and the activator) be separated. In other words, asuitable commercial product comprising hydrogen peroxide and alkalineactivator preferably has at least two independent parts, separated by abarrier. To this end, Ryles, et.al, U.S. Pat. No. 5,902,568 teaches ateeth-whitening toothpaste—a bi-phasic foam—in which hydrogen peroxideand sodium bicarbonate are stored separately and applied on thetoothbrush before use. However, although stable, this toothpaste has notbeen shown to have any appreciable teeth-whitening effect. The lack ofteeth whitening efficacy is due to the low strengths of the two activesand also to the method of their application to the teeth. Brushing ofthe teeth with such two-part (or biphasic) composition allows for only ashort exposure of the tooth surface to the teeth-bleaching composition,which is inadequate to affect significant teeth whitening.

Thus, even though sodium bicarbonate and hydrogen peroxide have beentaught as teeth-whitener, both independently and as a combination, therehas been no demonstration of significant improvement in teeth-whiteningusing products based on these teachings compared to products based onusing hydrogen peroxide alone as the bleaching agent. That is, there isno evidence to date that sodium bicarbonate (or any other alkalineactivating agent) increases the whitening efficacy of hydrogen peroxideteeth-whiteners. This is possibly due to one or more of: (1)concentrations of hydrogen peroxide and the alkaline activator, e.g.,sodium bicarbonate or another alkaline activator used are too low; (2)the device used for applying the combination is not effective; (3) theincipient oral chemistry does not allow full expression of the chemicalpotential of the combination, and; (4) the time of exposure of thesurfaces to the actives is insufficient. These shortcomings are thebasis for the lack of efficacy of prior art teeth-whitening methodsusing hydrogen peroxide and an alkaline activator, including those usingsodium bicarbonate as the activator.

The shortcomings of prior art teeth whitening chewing gum formulationsmay be summarized as follows: (A) The difficulty in formulating chewinggums having appreciable whitening activity and adequate shelf life dueto the vulnerability of anhydrous peroxides, particularly carbamideperoxide, in the presence of common ingredients of chewing gumformulations; (B) The difficulty of making peroxide containing chewinggums that allows for extrusion during manufacturing and that alsoproduces gums of adequate shelf life; (C) Technical difficultiesassociated with manufacturing teeth whitening chewing gums in two partsthat mix in the mouth during mastication; and (D) The poor whiteningeffect of teeth-whitening chewing gums of the prior art, which rendersthem not applicable for primary teeth-whitening, but only as potentiallyuseful for maintenance of teeth previously whitened by traditionalteeth-whiteners.

There is a need for a teeth-whitening chewing gum composition that hasappreciable whitening efficacy, stability (long shelf-life) incommercially packaged form, and consumer acceptable “mouth feel,” i.e.,a chewing gum that has enough oxidizing power to significantly whitenteeth in one treatment, that also has a shelf life suitable forcommercialization. And, there is a need for a bone-fide teeth-whitenerthat does not cause sensitivity of the soft and hard tissues of the oralcavity unlike other teeth-whiteners comprising carbamide peroxide.

SUMMARY OF THE INVENTION

Stable chewable gum-based compositions comprising a peroxide areprovided. The compositions have shelf life suitable forcommercialization in the form of packaged goods. Stability is achievedby choosing anhydrous ingredients (peroxide, fruit acid, and gum base),compounding under dry conditions, and using high amounts of the fruitacid (0.5-8 wt % of the composition; 5-800 mg, based on compositionweight of 1-10 g). Also provided are chewable compositions that arebiphasic, wherein one phase comprises the fruit acid-stabilized peroxidechewing gum composition and the other phase comprises a compositioncomprising a gum base and a source of bicarbonate ion. The two phasesmay be provided as one gum in which the phases are separated by abarrier layer, or as two independent chewable compositions. Thecomposition is activated by chewing the two phases at the same time. Thecompositions further include gum additives. In some embodiments, theperoxide containing composition is free of metal ions.

In one aspect, described herein is a chewable composition comprising ananhydrous chewing gum base having water content of about 1% by weight orless, an anhydrous fruit acid, a peroxide having water content of about2% by weight or less, and gum additives. In some embodiments, the fruitacid has a water content of less than 1% by weight.

In another aspect, the chewable gum composition (“the peroxidecomposition or gum”) further comprises glycerin or propylene glycol suchthat the gum is extrudable during manufacture.

In a further aspect, the chewable composition further comprises anabrasive material.

In yet another aspect, biphasic chewable compositions are provided whichcombine any of the above chewable compositions with another chewablecomposition that comprises a source of bicarbonate ion. In someembodiments, the source of bicarbonate ion is sodium bicarbonate.

Further, a teeth-whitening kit comprising a peroxide containingcomponent (component A) separated from a component comprising a sourceof bicarbonate ion (component B) is also provided.

In addition, methods of whitening teeth using the above-describedbiphasic chewable composition are provided.

The above-described biphasic chewable compositions are useful inprevention and remediation of many symptoms of oral diseases such asperiodontal disease, gingivitis. and halitosis, and maintenance ofhealthy gingiva and breath. As such, methods for prevention andremediation of the symptoms of these diseases are also provided.

Aspects of the invention will become readily apparent to those skilledin the art from the following detailed description, wherein onlyexemplary configurations of the teeth-whitening chewable compositions,kits comprising the compositions, and methods for teeth-whitening andprevention and remediation of symptoms of oral diseases using thecompositions are described.

As will be realized, the invention includes other and different aspectsof the disclosed teeth-whitening chewable compositions, kits comprisingthe compositions, and methods for teeth-whitening and prevention andremediation of symptoms of oral diseases using the compositions.Further, it will be realized that the various details presentedthroughout this disclosure are capable of modification in various otherrespects, all without departing from the spirit and scope of theinvention. Accordingly, the detailed description and the Examples thatfollow are to be regarded as illustrative in nature and not asrestrictive.

DETAILED DESCRIPTION OF THE INVENTION

Chewable compositions comprising a peroxide at levels effective forteeth-whitening and having shelf life suitable for a commercial packagedgoods are described. All ingredients are essentially anhydrous. Theamount of water (by weight) that may be present in the chewablecompositions comprising peroxide is about 5% or less, preferably about4% or less and more preferably about 2% or less. Teeth whiteningefficacy is a function of the concentration of the peroxide. The amountof peroxide per dosage of the teeth whitening treatment of the presentinvention is about 10-500 mg, preferably about 20-400 mg, morepreferably about 35-350 mg, and most preferably about 100-300 mg.

The peroxide may be selected from the following: hydrogen peroxide;peroxides generally of the first or second group of the periodic tableincluding calcium peroxide, calcium carbonate peroxide, sodium carbonateperoxide, zinc peroxide, strontium peroxide, other oxygen radicalgenerating agents; and preferably carbamide peroxide.

In the chewable compositions of the present disclosure, the peroxide isprovided with an anhydrous fruit acid. The term “fruit acid” as usedherein includes organic acids naturally occurring in any of the commonfruits. As used herein, by “anhydrous fruit acid” is meant a fruit acidhaving water content of less than 1%. The preferred fruit acid comprisescitric acid. Other fruit acids, including tartaric acid, malic acid,mandelic acid, adipic acid, fumaric acid, gluconic acid, lactic acid,succinic acid, oxalic acid, glycolic acid, and acetic acid may also beemployed either exclusively, or in combination with other fruit acids.The present disclosure provides chewable compositions that areextrudable during manufacture. These compositions preferably contain awetting agent, preferably glycerin. Other wetting agents that may beused include ethylene glycol, polyethylene glycol, propylene glycol,polypropylene glycol, fatty acid. esters; sorbitol, and combinations ormixtures thereof. The wetting agent is present at about 0.5-5% based onthe weight of the chewable composition.

Chewing gum base (“gum base”) can have different compositions describedin greater detail below. The amount of chewing gum base in the chewablecompositions described herein is about 10%-50% relative to the weight ofthe composition.

The compositions include one or more gum additives in an amountsufficient to make up 100% of a given composition. The additives can beconfectionary components such as flavoring agents and surfactants.Xylitol is a flavoring agent of choice and may be used in combinationwith sucralose or other non-saccharide or non-polyol sweeteners such asaspartame or saccharine to achieve the desired sweetening and flavoringeffect. The amount of xylitol, or other polyols such as sorbitol,mannitol, maltitol, etc., that may be used is about 10-70%, morepreferably about 15-55%, and most preferably from about 23-45% relativeto the weight of the chewable composition. The amount of sucralose, orother artificial or natural intense sweetening agents such as aspartame,or saccharine (or others including Stevia extracts and other naturallyoccurring intense sweeteners) that may be used is about 0.05 2%, morepreferably about 0.1%-1.5%, and most preferably from about 0.3-1.2%relative to the weight of the chewable composition. Gum additives aredescribed in greater detail below.

In some embodiments, the composition is free of metal ions.

Activation of the peroxide can be achieved by bringing the peroxide incontact with a chemical activator. For a shelf-stable peroxide-basedcommercial teeth-whitening product, the activating chemical agentpreferably does not contact the peroxide in any appreciable extent untilactivation is desired. A preferred way to achieve this objective is toprovide two compositions, one comprising a peroxide composition in whichthe peroxide is stabilized using fruit acid, and the other comprisingthe activator, such that upon chewing, the two compositions (or gum orphases), mix and the peroxide reacts to form the active, but short-livedchemical species that, ultimately, is the active agent for theteeth-bleaching reactions that result in teeth-whitening.

The present disclosure also provides chewable compositions having twophases (biphasic compositions) in which one phase (the “peroxide”phase), comprises the fruit acid-stabilized chewing gum compositioncomprising significant amounts of peroxide, and the other phase(“activator” phase) comprises a composition having an activator and agum base. In some embodiments, the activator is a metal bicarbonate saltor a combination of metal bicarbonate salts. In some embodiments, theactivator is a combination of metal carbonates and bicarbonates. Smallamounts of metal carbonate salts (e.g., sodium or potassium carbonate)may be employed to help stabilize the bicarbonate gum composition. Theamount of metal carbonate salt that may be used is about 0.001-1%,preferably about 0.01-0.1%, and more preferably from about 0.02-0.05% ofthe weight of the activator phase.

The amount of activator that may be used is about 5-65% and preferablyabout 5-30% based on the mass of the second chewable composition.

A preferred activator is bicarbonate ion and a preferred source ofbicarbonate ion is sodium bicarbonate. Potassium bicarbonate, a mixtureof potassium and sodium bicarbonates, as well as other metalbicarbonates may also be used.

The two phases are kept physically separated until they are chewedtogether. Chewing takes place for a period of time sufficient forcompletion of the reaction between the active agents of each phase.

A surprisingly high degree of teeth whitening was observed using thechewable teeth-whitening compositions described herein. Typically, inthe art of teeth-whitening using peroxide, an activator is expected toincrease whitening efficacy by about 0%-25% relative to un-activatedperoxide. In stark contrast, using the chewable gum compositionsdescribed herein, unexpectedly high teeth-whitening, on the order of100-1000%, was observed (see Example 6).

It was also surprisingly observed that the use of a source ofbicarbonate ions, preferably sodium bicarbonate, as the activator forteeth-whitening led to a significant reduction in sensitivity caused byperoxide. In these preferred embodiments, sodium bicarbonate is presentbetween 300 mg and 400 mg and carbamide peroxide is present at between200 mg and 300 mg.

In some embodiments, the weight of activator in the second chewablecomposition is at least three times the mass of the fruit acid used inthe complementary chewable composition comprising fruit acid stabilizedperoxide.

Generally, the amount of activator in an acceptable formulation of thepresent invention is an amount that is enough to maintain the pH of thesaliva at near neutral or slightly basic during and immediately afterchewing both gum compositions simultaneously.

Further, the present disclosure provides a multi-phasic tablet, whichcan be produced, for example, from a tablet press, common to the art ofpharmaceutical manufacturing of tablets. Such a tablet comprisesessentially the same ingredients in the same relative and absoluteamounts as the above-described chewable compositions, with additionalingredients added to aid in the tableting process—but without a wettingagent. These ingredients include binders, lubricators, coating, etc.Since these ingredients are well known to the pharmaceuticalmanufacturing art, they are not described here. In a single tabletcontaining both active agents, peroxide and activator, the agents areprovided in separate layers. The layers (phases) are separated from eachother by a barrier layer, which may be any inert substance that providesphysical separation of the two layers. The barrier layer, for example,may be an anhydrous chewable gum composition. Alternatively, it may be awax. Materials suitable as barrier layers are described in greaterdetail below.

In another acceptable multiphase composition, the peroxide phasecomposition may be microencapsulated with an inert micro-membrane. Suchmembranes are commonly used in the art of food chemistry, for example,for providing vitamin and other active agents in food products toachieve desired shelf-life. Prior art (see, for example, Gebreselassie,WO/2012/145611, hereby incorporated by reference) teachesmicroencapsulated chewing gum compositions, with details describedtherein of acceptable microencapsulation technologies.

Chewable Composition Chewable Composition Comprising Peroxide, Gum Base,and Fruit Acid

In one aspect, the present disclosure provides a chewable compositionfor teeth whitening, comprising an anhydrous chewing gum base havingwater content of about 1% or less, an anhydrous fruit acid, a peroxidehaving water content of about 2% or less, and one or more gum additives.The ratio of gum base: peroxide: fruit acid, in percent weight relativeto the composition, is about 10-50:1-20:0.5-8. The one or more gumadditives are present in an amount necessary to reach 100% of the weightof the composition, in some embodiments, the water content of thecomposition is about 2% or less. In some embodiments, the fruit acid iscitric acid. In some embodiments, the peroxide is carbamide peroxide. Insome embodiments, the mass of the composition is about 0.2 g to about 10g.

As used herein, the term “about” means within ±10%, preferably 5%, andmore preferably 1% of the given value.

Generally, the gum base constitutes between about 10-50 wt % (percentweight) of the chewable composition. In one embodiment, the gum base ispreset at about 20-35 wt % of the chewable composition.

In some embodiments, peroxide is present at about 1-20 wt % of thechewable composition. Alternatively, peroxide may be present at about4-20 wt %, at about 8-20 wt at about 12-20 wt %, at about 1-15 wt or atabout 5-15% of the chewable composition.

In some embodiments, fruit acid is present at about 0.5-8 wt of thechewable composition. Alternatively, fruit acid may be present at about1-7 wt %, at about 2-7 wt %, at about 3-7 wt %, at about 1-6 wt %, atabout 1-5 wt %, or at about 0.5-5 wt % of the chewable composition

Chewable Composition Comprising a Peroxide, Gum Base, Fruit Acid, and aWetting Agent

In another aspect, the chewable composition comprises a wetting agent inaddition to a peroxide, gum base, fruit acid, and gum additives. In someembodiments, the gum base, peroxide, and fruit acid are present in sameratio as in the above-described chewable composition comprising gumbase, peroxide, and fruit acid. In some embodiments, the fruit acid iscitric acid. In some embodiments, the peroxide is carbamide peroxide. Insome embodiments, the wetting agent is glycerin.

In some embodiments, the ratio of wetting agent: gum base: peroxide:fruit acid, in percent weight relative to the composition, is about0.5-5:10-50:1-20:0.5-8. In some embodiments, the water content of thecomposition is about 2% or less. In some embodiments, the mass of thecomposition is about 0.2 g to about 10 g. In some embodiments, the ratioof wetting agent: gum base: peroxide: fruit acid in percent weightrelative to the composition is about 1-3:20-35:5-15:0.5-8.

In some embodiments, the wetting agent is present at about 0.5-5 wt % ofthe chewable composition. Alternatively, the wetting agent may bepresent at about 1-5 wt %, at about 2-5%, at about 3-5 wt %, at about1-4 wt %, or at about 2-4 % of the chewable composition.

Chewable Composition Comprising Peroxide, Gum Base, Fruit Acid, aWetting Agent, and an Abrasive Material

In another aspect, the present disclosure provides a chewablecomposition comprising an abrasive material in addition to peroxide, gumbase, fruit acid, wetting agent, and one or more gum additives. In someembodiments, wetting agent, the gum base, peroxide, and the fruit acidare present in one or more of the same ratios as in the above-describedchewable composition comprising wetting agent, gum base, peroxide, fruitacid, and gum additives. In some embodiments, the fruit acid is citricacid. In some embodiments, the peroxide is carbamide peroxide In someembodiments, the wetting agent is glycerin.

In some embodiments, the ratio of the abrasive material: wetting agent:gum base: peroxide: fruit acid, in percent weight relative to thecomposition, is about 0.5-5:0.5-5:10-50:1-20:0.5-8.

In some embodiments, the abrasive material is present at about 0.5-5 wt% of the chewable composition. Alternatively, the abrasive material maybe present at about 1-5 wt %, at about 2-5%, at about 3-5 wt %, at about1-4 wt % or at about 2-4 wt % of the chewable composition.

Biphasic Chewable Composition Biphasic Chewable Composition ComprisingPeroxide, Gum Base, Fruit Acid, and an Activator

In another aspect, the present disclosure provides a chewablecomposition for teeth-whitening, comprising a first and a second regionseparated by a barrier layer.

The first region comprises the above-described chewable compositioncomprising peroxide, gum base, fruit acid, and one or more gumadditives.

The second region comprises a chewable composition having an activator(or source thereof), a gum base, and one or more gum additives. Theactivator may comprise a source of bicarbonate ions.

The activator (or source thereof) and the gum base, respectively, arepresent in a ratio of about 5-30:15-50 in percent weight relative to thesecond region. The one or more gum additives are present in an amountnecessary to reach 100% of the weight of the second region.

In some embodiments, the barrier layer comprises one or more componentsselected from the group consisting of lipids, proteins, carbohydrates,synthetic elastomers, polymers, wax, fat, and gum.

In some embodiments, the activator s bicarbonate ions and the source ofbicarbonate ion is sodium bicarbonate.

In some embodiments, the second region er comprises a metal carbonate atabout 0.001-1% of the weight of the second region.

In some embodiments, activator (or source thereof) is present at about5-30 wt % of the second region. Alternatively, the activator (or sourcethereof) may be present at about 10-30 wt %, at about 15-30 wt %, atabout 20-30 wt %, at about 5-25 wt %, at about 5-20 wt %, at about 5-15wt %, at about 10-25 wt %, or at about 15-25 wt % the second region.

In some embodiments, the ratio of fruit acid: peroxide: activator, bymass, is about 0.5-5:5-30:15-45.

In some embodiments, the fruit acid is citric acid.

In some embodiments, the peroxide is carbamide peroxide.

In some embodiments, activator is present at three times or more theamount of the fruit acid.

Biphasic Chewable Composition Comprising a Wetting Agent, Peroxide, GumBase, Fruit Acid, and an Activator

In one aspect, provided herein is another chewable composition forteeth-whitening, comprising a first and a second region separated by abarrier layer.

The first region comprises the above-described chewable compositioncomprising a wetting agent, peroxide, fruit acid, and one or more gumadditives.

The second region comprises a chewable composition having an activator(or source thereof), a gum base, and one or more gum additives. Theactivator may be bicarbonate ions.

The activator (or source thereof) and the gum base, respectively, arepresent in a ratio of about 5-30:15-50 in percent weight relative to thesecond region. The one or more gum additives are present in an amountnecessary to reach 100% of the weight of the second region.

In some embodiments, the barrier layer comprises one or more componentsselected from the group consisting of lipids, proteins, carbohydrates,synthetic elastomers, polymers, wax, fat, and gum.

In some embodiments, the activator is bicarbonate ions and the source ofbicarbonate ion is sodium bicarbonate.

In some embodiments, the second region further comprises a metalcarbonate at about 0.001-1% of the weight of the second region.

In some embodiments, the activator (or source thereof) is present atabout 5-30 wt % of the second region. Alternatively, activator (orsource thereof) may be present at about 10-30 wt %, at about 1:5-30 wt%, at about 20-30 wt %, at about 5-25 wt %, wt %, 5-15 wt %, at about10-25 wt %. or at about 15-25 wt % the second region.

In some embodiments, the ratio of fruit acid: peroxide: activator (orsource of activator), by mass, is about 0.51 .5:3-7:5-10.

In some embodiments, the fruit acid is citric acid.

In some embodiments, the peroxide is carbamide peroxide.

In some embodiments, the activator (or source thereof) is present atthree times or more the amount of the fruit acid.

Biphasic Chewable Composition Comprising an Abrasive Material, a WettingAgent, Peroxide, Gum Base, Fruit Acid, and an Activator or Source of anActivator

In yet another aspect, the present disclosure provides a chewablecomposition for teeth-whitening, comprising a first and a second regionseparated by a barrier layer.

The first region comprises the above-described chewable compositioncomprising an abrasive material, a wetting agent, peroxide, fruit acid,and one or more gum additives.

The second region comprises a chewable composition having an activator(or source thereof), a gum base, and one or more gum additives. Theactivator may be bicarbonate ions.

The activator (or source thereof) and the gum base, respectively, arepresent in a ratio of about 5-30:15-50 in percent weight relative to thesecond region. The one or more gum additives are present in an amountnecessary to reach 100% of the weight of the second region.

In some embodiments, the barrier layer comprises one or more componentsselected from the group consisting of lipids, proteins, carbohydrates,synthetic elastomers, polymers, wax, fat, and gum.

In some embodiments, the activator is bicarbonate ions and the source ofbicarbonate ions is sodium bicarbonate.

In some embodiments, the second region further comprises a metalcarbonate at about 0.001-1% of the weight of the second region.

In some embodiments, activator (or source thereof) is present at about5-30 wt % of the second region. Alternatively, activator (or sourcethereof) may be present at about 10-30 wt %, at about 15-30 wt %, atabout 20-30 wt %, at about 5-25 wt %, at about 5-20 wt %, at about 5-15wt %, at about 10-25 wt %, or at about 15-25 wt % the second region.

In some embodiments, the ratio of fruit acid peroxide: activator (orsource thereof) by mass, is about 0.5-5:5-20:10-35.

In some embodiments, the fruit acid is citric acid.

In some embodiments, the peroxide is carbamide peroxide.

In some embodiments, the activator (or source thereof) is present atthree times or more the amount of the fruit acid.

Teeth-Whitening Kit

In one aspect, the present disclosure provides a teeth-whitening kitcomprising a component A separated from component B. Component Acomprises the chewable composition according to any of theabove-described chewable composition comprising (1) peroxide, gum base,a fruit acid, and one or more gum additives; or (2) a wetting agent,peroxide, gum base, a fruit acid, and one or more gum additives; or (3)an abrasive material, a wetting agent, peroxide, gum base, a fruit acid,and one or more gum additives. Component B comprises a chewablecomposition comprising a gum base, an activator (or source thereof), andone or more gum additives. The one or more gum additives are present inan amount necessary to reach 100% of the weight of the second region.

In this kit, the ratio of the activator (or source thereof):gum base, inpercent weight relative to component B, is about 5-30:15-50. The kitfurther includes instructions for use to achieve teeth-whitening.

In some embodiments, the activator is bicarbonate ions, and the sourceof bicarbonate ions is sodium bicarbonate.

In some embodiments, component B further comprises a metal carbonate atabout 0.001-1% of the weight of component B.

In some embodiments, the relative amounts of component A and component Bper dose of teeth-whitening treatment is such that activator (or sourcethereof) is present at three times or more the amount of the fruit acid.

In some embodiments, the ratio of fruit acid: peroxide: activator (orsource thereto), by mass is about 0.5-5:5-20:10-35.

In some embodiments, the fruit acid is citric acid.

In some embodiments, the peroxide is carbamide peroxide.

In some embodiments, the relative amounts of component A and component Bper dose is such that pH of a water extract of the composition is atleast about 7.

Teeth-Whitening Method

In one aspect, the present disclosure provides a method for whiteningteeth in a human in need thereof. The method comprises placing in theoral cavity of the human a single composition according to any of thethree above-described biphasic compositions; and chewing the compositionfor about 1 to about 30 minutes. The total weight of the composition isabout 1 g to about 10 g and the chewing provides about 20 mg to about400 mg hydrogen peroxide equivalents.

In some embodiments, the activator is bicarbonate ions and the source ofbicarbonate ion is sodium bicarbonate. In some embodiments, the peroxideis carbamide peroxide.

In some embodiments, the second region of the single chewablecomposition further comprises a metal carbonate at about 0.001-1% of theweight of the second region.

In some embodiments, the ratio of fruit acid: peroxide: activator(source thereof), by mass is about 0.5-5:5-20:10-35.

In some embodiments, the fruit acid is citric acid.

In some embodiments, in the chewable composition, activator (sourcethereof) is present at three times or more the amount of the fruit acid.

In another aspect, the present disclosure provides another method forwhitening teeth in a human in need thereof. The method comprises placingin the oral cavity of the human a first composition and a secondcomposition; and chewing the compositions together for about 1 to about30 minutes. The first chewable composition is one of the above-describedchewable compositions comprising (1) peroxide, gum base, a fruit acid,and one or more gum additives; or (2) a wetting agent, peroxide, gumbase, a fruit acid one or more gum additives; or (3) an abrasivematerial, a wetting agent, peroxide, gum base, a fruit acid, and one ormore gum additives. The second composition comprises a chewablecomposition comprising a gum base, an activator (or source of anactivator), and one or more additives. The one or more gum additives arepresent in an amount necessary to reach 100% of the weight of the secondcomposition. The ratio of activator (or source thereof): gum base, inpercent weight relative to the second composition is about 5-30:15-50.The total weight of the compositions is about 1 g to about 10 g and thechewing provides about 20 mg to about 400 mg hydrogen peroxideequivalents.

In some embodiments, the activator is bicarbonate ions and the source ofbicarbonate ion is sodium bicarbonate.

In some embodiments, the second composition further comprises a metalcarbonate at about 0.001-1% of the weight of the second composition.

In some embodiments, in the first and the second composition combined,the ratio of fruit acid: peroxide: activator (or source thereof), bymass is about 0.5-5:5-20:10-35. In some embodiments, the fruit acid iscitric acid.

In some embodiments, the peroxide is carbamide peroxide.

In some embodiments, activator is present at three times or more theamount of the fruit acid.

In some embodiments, the pH of the saliva of the human during chewing isabout 5.5 to about 7.

Remedial of Symptoms of Periodontal Disease

In one aspect, the present disclosure provides a method for remedial ofperiodontal disease in a human in need thereof, the method comprising:(a) placing in the oral cavity of the human a single chewablecomposition according to any of the three above-described biphasiccompositions; and (b) chewing the composition for about 1 to about 30minutes; wherein the total weight of the composition is about 1 g toabout 10 g and the chewing provides about 20 mg to about 400 mg hydrogenperoxide equivalents.

In some embodiments, steps (a) and (b) are repeated. For example, thesteps are performed one to five times a day for a period of 2-10 days.In some embodiments, the activator is bicarbonate ions and the source ofbicarbonate ion is sodium bicarbonate. In some embodiments, the ratio offruit acid: peroxide: activator (or source thereof), by mass is about0.5-5:5-20:10-35. In some embodiments, the fruit acid is citric acid. Insome embodiments the peroxide is carbamide peroxide. In someembodiments, in the chewable composition, the activator (or sourcethereof) is present at three times or more the amount of the fruit acid.In some embodiments, the pH of the saliva of the human during chewing isabout 5.5 to about 7.

In another aspect, the present disclosure provides another method forremedial of periodontal disease in a human in need thereof. The methodcomprises (a) placing in the oral cavity of the human a firstcomposition and a second composition; and (b) chewing the compositionstogether for about 1 to about 30 minutes. The first chewable compositionis one of the above-described chewable compositions comprising (1)peroxide, gum base, a fruit acid, and one or more gum additives; or (2)a wetting agent, peroxide, gum base, a fruit acid one or more gumadditives; or (3) an abrasive material, a wetting agent, peroxide, gumbase, a fruit acid, and one or more gum additives. The secondcomposition comprises a chewable composition comprising a gum base, anactivator (or source thereof), and one or more additives. The one ormore gum additives are present in an amount necessary to reach 100 % ofthe weight of the second composition. The ratio of activator (or sourcethereof): gum base, in percent weight relative to the second compositionis about 5-30:15-50. The total weight of the compositions is about 1 gto about 10 g and the chewing provides about 20 mg to about 400 mghydrogen peroxide equivalents.

In some embodiments, steps (a) and (h) are repeated, for example thesteps are performed one to five times a day for a period of 2-10 days.In some embodiments, the activator is bicarbonate ions and the source ofbicarbonate ion is sodium bicarbonate. In some embodiments, the ratio offruit acid: peroxide: activator (or source thereof), by mass is about0.5-5:5-20:10-35. In some embodiments, the fruit acid is citric acid. Insome embodiments the peroxide is carbamide peroxide. in someembodiments, in the chewable composition, the activator is present atthree times or more the amount of the fruit acid. In some embodiments,the pH of the saliva of the human during chewing is about 5.5 to about7.

Gum Base

Typically, the gum base contains elastomers (rubbers). The elastomersemployed in the gum base will vary greatly depending upon variousfactors such as the type of gum base desired, the consistency of gumcomposition desired and the other components used in the composition tomake the final chewing gum product. The elastomer may be anywater-insoluble polymer known in the art and includes those gum polymersutilized for chewing gums and bubble gums. Illustrative examples ofsuitable polymers in gum bases include both natural and syntheticelastomers. For example, polymers which are suitable in gum basecompositions include, without limitation, natural substances (ofvegetable origin) such as chicle, natural rubber, crown gum, nispero,rosidinha, jelutong, perillo, niger gutta, tuna, balata, guttapercha,lechi capsi, sorva, gutta kay, and the like, and combinations thereof.Examples of synthetic elastomers include, without limitation,styrene-butadiene copolymers (SBR), polyisbbutylene,isobutylene-isoprene copolymers, polyethylene, polyvinyl acetate and thelike, and combinations thereof. A preferred gum base for use in thechewable compositions described herein is known by the tradename“NOVA-T” and is made by CAFOSA corporation. Another preferred gum baseis “PIB-T” made by Eurobase.

Additional useful polymers include: crosslinked polyvinyl pyrrolidone,polymethylmethacrylate; copolymers of lactic acid,polyhydroxyalkanoates, plasticized ethylcellulose, polyvinylacetatephthalate, and combinations thereof.

The amount of elastomer employed in the gum base may vary depending uponvarious factors such as the type of gum base used, the consistency ofthe gum composition desired and the other components used in thecomposition to make the final chewing gum product.

In some embodiments, the gum base may include wax. Wax softens thepolymeric elastomer mixture and improves the elasticity of the gum base.When present, the wax(es) employed will have a melting point below about60° C., and preferably between about 45° C. and about 55° C. The lowmelting wax may be a paraffin wax. The wax may be present in the gumbase in an amount from about 6% to about 10%, and preferably from about7% to about 9.5%, by weight of the gum base.

In addition to the low melting point waxes, waxes having a highermelting point may be used in the gum base in amounts up to about 5%, byweight of the gum base. Such high melting waxes include beeswax,vegetable wax, candelilla wax, carnuba wax, most petroleum waxes, andthe like, and mixtures thereof.

In addition to the components set out above, the gum base may include avariety of other ingredients, such as components selected from elastomersolvents, emulsifiers, plasticizers, fillers, and mixtures thereof.

The gum base may contain elastomer solvents to aid in softening theelastomer component. Such elastomer solvents may include those elastomersolvents known in the art, for example, terpinene resins such aspolymers of alpha-pinene or beta-pinene, methyl, glycerol andpentaerythritol esters of rosins and modified rosins and gums such ashydrogenated, dimerized and polymerized rosins, and mixtures thereof.Examples of elastomer solvents suitable for use herein include thepentaerythritol ester of partially hydrogenated wood and gum rosin, thepentaerythritol ester of wood and gum rosin, the glycerol ester of woodrosin, the glycerol ester of partially dimerized wood and gum rosin, theglycerol ester of polymerized wood and gum rosin, the glycerol ester oftall oil rosin, the glycerol ester of wood and gum rosin and thepartially hydrogenated wood and gum rosin and the partially hydrogenatedmethyl ester of wood and rosin, and the like, and mixtures thereof. Theelastomer solvent may be employed in the gum base in amounts from about2% to about 15%, and preferably from about 7% to about 11%, by weight ofthe gum base.

The gum base may also include emulsifiers which aid in dispersing theimmiscible components into a single stable system. The emulsifiersuseful in this invention include glyceryl monostearate, lecithin, fattyacid monoglycerides, diglycerides, propylene glycol monostearate, andthe like, and mixtures thereof. The emulsifier may be employed inamounts from about 2% to about 15%, and more specifically, from about 7%to about 11%, by weight of the gum base.

The gum base may also include plasticizers or softeners to provide avariety of desirable textures and consistency properties. Because of thelow molecular weight of these ingredients, the plasticizers andsofteners can penetrate the fundamental structure of the gum base makingit plastic and less viscous. Useful plasticizers and softeners includelanolin, palmitic acid, oleic acid, stearic acid, sodium stearate,potassium stearate, glyceryl triacetate, glyceryl glyceryl monostearate,propylene glycol monostearate, acetylated monoglyceride, glycerine, andthe like, and mixtures thereof. Waxes, for example, natural andsynthetic waxes, hydrogenated vegetable oils, petroleum waxes such aspolyurethane waxes, polyethylene waxes, paraffin waxes, microcrystallinewaxes, fatty waxes, sorbitan monostearate, tallow, propylene glycol,mixtures thereof, and the like, may also be incorporated into the gumbase. The plasticizers and softeners are generally employed in the gumbase in amounts up to about 20% by weight of the gum base, and morespecifically in amounts from about 9% to about 17%, by weight of the gumbase.

Plasticizers also include are the hydrogenated vegetable oils andinclude soybean oil and cottonseed oil which may be employed alone or incombination. These plasticizers provide the gum base with good textureand soft chew characteristics. These plasticizers and softeners aregenerally employed in amounts from about 5% to about 14%, and morespecifically in amounts from about 5% to about 13.5%, by weight of thegum base.

Anhydrous glycerin may also be employed as a softening agent, such asthe commercially available United States Pharmacopeia (USP) grade.Glycerin is a syrupy liquid with a sweet warm taste and has a sweetnessof about 60% of that of cane sugar. Because glycerin is hygroscopic, theanhydrous glycerin may be maintained under anhydrous conditionsthroughout the preparation of the chewing gum composition.

In some embodiments, the gum base of this invention may also includeeffective amounts of bulking agents such as mineral adjuvants which mayserve as fillers and textural agents. Useful mineral adjuvants includecalcium carbonate, magnesium carbonate, alumina, aluminum hydroxide,aluminum silicate, talc, tricalcium phosphate, dicalcium phosphate,calcium sulfate and the like, and mixtures thereof. These fillers oradjuvants may be used in the gum base compositions in various amounts.The amount of filler, may be present in an amount from about zero toabout 40%, and more specifically from about zero to about 30%, by weightof the gum base. In some embodiments, the amount of filler will be fromabout zero to about 15%, more specifically from about 3% to about 11%.

A variety of traditional ingredients may be optionally included in thegum base in effective amounts such as coloring agents, antioxidants,preservatives, flavoring agents, and the like. example, titanium dioxideand other dyes suitable for food, drug and cosmetic applications, knownas F. D. & C. dyes, may be utilized. An anti-oxidant such as butylatedhydroxytoluene (BHT), butylated hydroxyanisole (BHA), propyl gallate,and mixtures thereof, may also be included. Other conventional chewinggum additives known to one having ordinary skill in the chewing gum artmay also be used in the gum base.

Abrasive Material

Suitable abrasive materials include silicas, aluminas, phosphates,carbonates and combinations thereof. In some embodiments, the abrasiveagent is a silica selected from: precipitated amorphous silica, silicagels, and combinations thereof. In some embodiments the abrasivematerial is selected from the following: calcium carbonate, sodiumbicarbonate, sodium metaphosphate, potassium metaphosphate, tricalciumphosphate, dehydrated dicalcium phosphate, and combinations thereof.

The abrasive material contemplated for use in the chewable compositioncan be any material which does not excessively abrade dentin. However,silica dental abrasives have unique benefits of exceptional dentalcleaning and polishing performance without unduly abrading tooth enamelor dentin. Silica is the preferred abrasive agent for the peroxidecontaining composition (or phase/layer) of the present invention. Othersuitable abrasive materials, including aluminas, phosphates, carbonatesand combinations thereof, may be employed as abrasive agents in thebicarbonate containing composition (or phase/layer) of the presentinvention.

The silica abrasive materials described herein, as well as otherabrasive material, generally have an average particle size rangingbetween about 0.1 to about 30 microns, and preferably from about 5 toabout 15 microns. The abrasive can be precipitated amorphous silica orsilica gels such as the silica xerogels described in U.S. Pat. No.3,538,230 to Pader, et al. and U.S. Pat. No. 3,862,307 to DiGiulio, bothincorporated herein by reference in their entireties. Preferred are thesilica xerogels marketed under the trade name “Syloid” by the W. R.Grace &. Company, Davison Chemical Division. Also preferred are theprecipitated amorphous silica materials, such as those marketed by theJ. M. Huber Corporation under the trade name “Zeodent”, particularly thesilica carrying the designation “Zeodent 113”. The types of silicadental abrasives useful in the present invention are described in detailin U.S. Pat. No. 4,340,583 to Wason, incorporated herein by reference inits entirety.

Gum Additives

Additives conventionally used in chewing gums are known to a personskilled in the art of manufacturing chewing gums and may be used in thecompositions described herein. Such additives include bulk sweeteners,high intensity sweeteners, flavoring agents, softeners, emulsifiers,coloring agents, binding agents, acidulants, fillers, antioxidants, andother components such as pharmaceutically or biologically activesubstances, that confer desired properties to the finished chewing gumproduct.

Examples of suitable sweeteners are listed in the following. Suitablebulk sweeteners include e.g. both sugar and non-sugar components. Usefulsugar sweeteners are saccharide-containing components commonly known inthe chewing gum art including, but not limited to, sucrose, dextrose,maltose, dextrins, trehalose, D-tagatose, dried invert sugar, fructose,levulose, galactose, corn syrup solids, and the like, alone or incombination. Sorbitol can be used as a non-sugar sweetener. Other usefulnon-sugar sweeteners include, but are not limited to, other sugaralcohols such as mannitol, xylitol, hydrogenated starch hydrolysates,maltitol, isomaltol, erythritol, lactitol and the like, alone or incombination. High intensity artificial sweetening agents can also beused alone or in combination with the above sweeteners. Preferred highintensity sweeteners include, but are not limited to sucralose,aspartame, salts of acesulfame, alitame, saccharin and its salts,neotame, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones,thaumatin, monellin, sterioside and the like, alone or in combination.In order to provide longer lasting sweetness and flavour perception, itmay be desirable to encapsulate or otherwise control the release of atleast a portion of the artificial sweetener. Techniques such as wetgranulation, wax granulation, spray drying, spray chilling, fluid bedcoating, coascervation, encapsulation in yeast cells and fibre extrusionmay be used to achieve desired release characteristics. Encapsulation ofsweetening agents can also be provided e.g. using as the encapsulationagent another chewing gum component such as a resinous compound.

If a low-calorie gum is desired, a low-caloric bulking agent can beused. Examples of low caloric bulking agents include polydextrose,Raftilose, Raffilin, Inuline, fruaooligosaccharides (NutraFlora®),palatinose oligosaccharided; guar gum hydrolysates (e.g. Sun Fiber®) orindigestible dextrins (e.g. Fibersol®). However, otherlow-calorie-bulking agents can be used.

Further chewing gum additives which may be included in the chewing gummixture processed in the present process include surfactants and/orsolubilizers. Anionic, cationic, amphoteric or non-ionic solubilizerscan be used. Suitable solubilizers include lecithins, poly6xyethylenestearate, polyoxyethylene sorbitan fatty acid esters, fatty acid salts,mono and diacetyl tartaric acid esters of mono and diglycerides ofedible fatty acids, citric acid esters of mono and diglycerides ofedible fatty acids, saccharose esters of fatty acids, polyglycerolesters of fatty acids, polyglycerol esters of interesterified castor oilacid (E476), sodium stearoyllatylate, sodium lauryl sulfate and sorbitanesters of fatty acids and polyoxyethylated hydrogenated castor oil (e.g.the product sold under the trade name CREMOPHOR), block copolymers ofethylene oxide and propylene oxide (e.g. products sold under trade namesPLURONIC and POLOXAMER), polyoxyethylene fatty alcohol ethers,polyoxyethylene sorbitan fatty acid esters, sorbitan esters of fattyacids and polyoxyethylene steraric acid esters.

Particularly suitable solubilizers include polyoxyethylene stearates,such as for instance polyoxyethylene(8)stearate and polyoxyethylene(40)stearate, the polyoxyethylene sorbitan fatty acid esterssold under the trade name TWEEN, for instance TWEEN 20 (monolaurate),TWEEN 80 (monooleate), TWEEN 40 (monopalmitate), TWEEN 60 (monostearate)or TWEEN 65 (tristearate), mono and diacetyl tartaric acid esters ofmono and diglycerides of edible fatty acids, citric acid esters of monoand diglycerides of edible fatty acids, sodium stearoyillactylate,sodium laurylsulfate, polyoxyethylated hydrogenated castor oil,blockcopolymers of ethylene oxide and propyleneoxide and polyoxyethylenefatty alcohol ether. The solubilizer may either be a single compound ora combination of several compounds.

Aroma agents and flavoring agents which are useful in the chewablecompositions described herein include natural and synthetic flavoringsin the form of freeze-dried natural vegetable components, essentialoils, essences, extracts, powders, including acids and other substancescapable of affecting the taste profile. Examples of liquid and powderedflavorings include coconut, coffee, chocolate, vanilla, grape fruit,orange, lime, menthol, liquorice, caramel aroma, honey aroma, peanut,walnut, cashew, hazelnut, almonds, pineapple, strawberry, raspberry,tropical fruits, cherries, cinnamon, peppermint, wintergreen, spearmint,eucalyptus, and mint, fruit essence such as from apple, pear, peach,strawberry, apricot, raspberry, cherry, pineapple, and plum essence. Theessential oils include peppermint, spearmint, menthol, eucalyptus, cloveoil, bay oil, anise, thyme, cedar leaf oil, nutmeg, and oils of thefruits mentioned above.

Various synthetic flavors, such as mixed fruit flavor may also be used.Sorbitol can be used as a non-sugar sweetener. Other useful non-sugarsweeteners include, but are not limited to, other sugar alcohols such asmannitol, xylitol, hydrogenated starch hydrolysates, maltitol,isomaltol, erythritol, lactitol and the like, alone or in combination.

Barrier Layer

The barrier layer in the chewable compositions of the present disclosuremay include lipids, proteins, carbohydrates, synthetic elastomers, andcombinations thereof. Synthetic elastomers may include, but are notlimited to, styrene-butadiene copolymers (SBR), polyisobutylene,isobutylene-isoprene copolymers, polyethylene, polyvinyl acetate andcombinations thereof. In some embodiments, the barrier layer has athickness range of about 0.1 mm to about 1 cm.

The barrier layer may include a non-saccharide “candy” gum composition.The barrier layer may include a substantially continuous amorphouschewing gum candy matrix. Such a barrier layer has low porosity. A candygum composition may be formed from a mixture of a melted gum base and acooked hard “candy” syrup. In particular, in some embodiments, the candygum composition is formed from a mixture of a melted chewing gum baseand a cooked polyol. Such materials may normally contain from 0.1% to5.0% water. The syrup component is to be prepared from non-fermentablesugars such as sorbitol, mannitol, xylitol, erythritol, lactitol andmaltitol and syrups thereof, such as hydrogenated starch hydrolysatesand sorbitol solutions. The amorphous polyols are useful for preparingan amorphous barrier layer with decreased porosity. Methods of preparingcandy gum compositions suitable for use as the barrier layercompositions are described, for example, in U.S. Pat. No. 4,741,905, theentire contents of which are incorporated herein by reference.

In some embodiments the barrier layer is formed as a typical chewing gumcomposition having low water content, that comprises similar amounts ofgum base and polyol sweetening and filling agent. Xylitol is thepreferred polyol. In particular, a suitable barrier layer having lowporosity may be prepared from a composition including at least 25-65% byweight of a gum base and about 25%-65% by weight of polyol. Fillers caninclude, for example, bulking agents (e.g., bulk sweeteners, mineraladjuvants, carriers and extenders), flavors and high intensitysweeteners.

In some embodiments the barrier layer is formed from a high gum base,low filler composition. In particular, a suitable barrier layer havinglow porosity may be prepared from a composition including at least 50%by weight of a gum base and less than 40% by weight of fillers. In someembodiments, the filler is present in the barrier layer in an amount ofabout 20 to about 40% by weight of the barrier layer. Fillers caninclude, for example, bulking agents (e.g., bulk sweeteners, mineraladjuvants, carriers and extenders), flavors and high intensitysweeteners. In some embodiments, the barrier layer is formed from acomposition that includes less than 5% by weight of xylitol or othersugar alcohols and combinations thereof. In some other embodiments, thebarrier layer composition includes no bulk sweeteners. Examples of highgum base, low filler gum compositions which are suitable for forming thebarrier layer in the present invention are provided in InternationalPublication Number WO 02/094033 A1, the entire contents of which areincorporated herein by reference.

The barrier layer may be formed from a hydrophobic substance. In someembodiments, the barrier layer is formed form at least one lipid, suchas a fat or wax. Fats may include, for example, hydrogenated oils orsaturated fatty acids. Waxes may include, for example, paraffin wax orbeeswax.

In some other embodiments, the barrier layer may be formed from one ormore hydrophilic biopolymers to serve as an effective barrier layeragainst these hydrophobic compounds. Examples of suitable hydrophilicbarriers include, but are not limited to, gluten, milk proteins,gelatin, starch, pectinates and cellulose-ethers.

In other embodiments, the harrier layer may be formed from a combinationof hydrophobic and hydrophilic substances. For example, lipids andbiopolymers can be combined to form an effective barrier layer. Suitablebiopolymers include, but are not limited to, proteins andpolysaccharides. For example, these biopolymers include, but are notlimited to, gluten, milk proteins, gelatin, starch, pectinates andcellulose-ethers. In some embodiments, a barrier layer formed from acombination of hydrophobic and hydrophilic substances may be anemulsion-based barrier layer.

In some embodiments, the barrier layer includes at least one gellinghydrocolloid. Hydrocolloids are hydrophilic polymers of vegetable,animal, microbial or synthetic origin that generally contain manyhydroxyl groups and may be polyelectrolytes. Examples of gellinghydrocolloids which may be used in the barrier layer include, but arenot limited to, agar, alginate, carrageenan, cellulose ethers, such ashydroxypropylmethyl cellulose and methylcellulose, gelatins, gellan gum,locust bean gum, pectin, starches, xanthan gum and combinations thereof.

Disclosure of suitable barrier layers may be found in the applicationUS20060263476, which is hereby incorporated by reference.

EXAMPLES Example 1. Discovery of Stability of Chewable CompositionComprising Carbamide Peroxide using Fruit Acid as a Stabilizing Agent

Sixteen different chewable compositions having different amounts ofcitric acid and carbamide peroxide were tested for stability.Combinations containing four different levels of citric acid (0%, 1%,2%, and 5% relative to the weight of the composition), each combinedwith one of four different levels of carbamide peroxide (1.5%, 5.0%,10.0%, 15.0% relative to the weight of the composition) were prepared.See Table 1 below, compositions A-P.

Ingredient Amount Carbamide peroxide variable (mg) Gum base 900 mgXylitol variable (mg) Spearmint oil (spray-dried)  20 mg Sucralose  30mg Glycerin  50 mg Citric Acid variable (mg) Silica  40 mg

TABLE 1 Chewable compositions (2.0 g) having different concentrations ofcitric acid and carbamide peroxide Citric Acid Peroxide gum (anhydrous)1.5% peroxide 5% peroxide 10% peroxide 15% peroxide 1% A D G J 2% B E HK 5% C F I L 0% M N O P

Other than the citric acid and the carbamide peroxide, each compositionhad the same composition. Any mass change due to change in mass ofeither citric acid or carbamide peroxide was compensated by the additionof xylitol. Stability was assessed by direct titration of hydrogenperoxide (starch iodide method), and also by pH, as well as bysubjective measurements of taste and visual characteristics. The sampleswere stored as packets sealed under argon in a temperature andhumidity-controlled environment of 35° C. and 60% humidity. The resultsof stability assessment are shown in Table 2 below.

TABLE 2 Stability of peroxide gum as a function of citric acidconcentration Citric Acid- % H₂O₂ Peroxide gum 0 30 90 180 360combination (days) (days) (days) (days) (days) A 0.5 0.4 0.3 0.2 0.2 B0.5 0.5 0.5 0.5 0.4 C 0.5 0.5 0.5 0.5 0.4 D 1.6 1.4 1.2 1 0.9 E 1.6 1.61.6 1.5 1.4 F 1.6 1.6 1.6 1.6 1.5 G 3.3 2.9 2.8 2.7 2.5 H 3.3 3.3 3.23.1 3.1 I 3.3 3.3 3.2 3.2 3.1 J 5.2 4.9 4.5 4.4 3.2 K 5.2 5.1 5.1 5 4.9L 5.2 5.1 5.1 5 5 M 0.5 0.3 0.2 0 0 N 1.6 1.1 0.6 0.1 0 O 3.3 2.4 1.80.9 0.1 P 5.2 4.1 2.1 0.9 0.3

The results show conclusively that of the sixteen combinations, eight,namely, B, C, E, F, H, I, K, and L demonstrated appreciable stability,i.e., demonstrated shelf life suitable for commercialization. Notably,each of these eight chewable gum composition compositions has citricacid >or =2%,

Example 2. Stable Carbamide Peroxide Gum Prepared by Tablet PressTechnology

Ingredient Amount Carbamide peroxide 250 mg Gum base 900 mg Xylitol 850mg Sorbitol 500 mg Peppermint oil (spray-dried)  25 mg Sucralose  30 mgCitric Acid  50 mg Magnesium Stearate  75 mg Stearic Acid 100 mgMicrocrystalline Cellulose 125 mg

The above-listed ingredients were combined and blended in a ribbonblender at slow speed until homogeneous, then submitted immediately to atablet press. Circular tablets were ejected at about 2.6 grams percomposition.

Example 3. Stable Carbamide Peroxide Chewable Gum Composition Preparedby Extrusion

The ingredients listed below, in the amounts shown, were used to producechewable gum compositions by extrusion.

Ingredient Amount Carbamide peroxide 330 mg Gum base (“PIB/NOVA-T”) 900mg Xylitol 700 mg Spearmint oil (spray-dried)  20 mg Sucralose  30 mgCitric Acid  50 mg Glycerin  60 mg Silica  40 mg

Example 4. Two Gum Composition Formulations for Maximum Teeth-Whitening

Thirty-two different combinations of carbamide peroxide containingchewable compositions, namely (“peroxide gum”), B, C, E, F, H, I, K, andL (see Example 1) and sodium bicarbonate containing chewablecompositions (“bicarbonate gum”) having the formulation shown below weretested for teeth-whitening efficacy.

Peroxide containing gum (made by extrusion)

Ingredient Amount Carbamide peroxide variable (mg) Gumbase(“PIB-T/NOVA-T”) 700 mg Xylitol variable (mg) Spearmint oil(spray-dried)  20 mg Sucralose  30 mg Glycerin  50 mg Citric Addvariable (mg) Silica  50 mg

Procedure

-   1) Gum base and xylitol were added to a warm mixer and mixing    started.-   2) Upon softening of the resulting mixture, about half of the    remaining xylitol was added and mixing continued for 2 minutes.-   3) Citric acid, silicon dioxide, and carbamide peroxide were added    and mixing continued for approximately 2 minutes.-   4) Glycerin and coolant were added and mixing continued for    approximately 1.5 minutes.-   5) Remaining xylitol was gradually added and mixing continued for    approximately 2 minutes.-   6) Sucralose was added and mixing continued for approximately for 1    minute.-   7) Flavor was added and mixing continued for 2-3 minutes until batch    was uniform. Upon cooling, rectangular pieces, 2.0-2.2g/piece, were    extruded.    Bicarbonate Containing Gum (made by Extrusion)

Ingredient Amount Sodium bicarbonate variable (mg) Amorphous silica  20mg Gum base (“PIB/NOVA-T”) ( 710 mg Spray dried peppermint oil 100 mgMaltitol syrup 250 mg Xylitol variable (mg) Calcium carbonate  5 mgSodium carbonate  5 mg Glycerol  20 mg Coating (xylitol) 325 mg Lecithin 2 mg Titanium dioxide  5 mg * Xylitol was added in place of sodiumbicarbonate, to achieve appropriate equal masses of the “bicarbonate”chewable gum composition

Procedure

-   1) Gum base, xylitol, and titanium dioxide were added to a warm    mixer and mixing started.-   2) Upon softening of the resulting mixture, about half of the    remaining xylitol was added and mixing continued for 2 minutes.-   3) Coolant, sucralose, and sodium bicarbonate/silicon dioxide were    added to the mixture and mixing continued for about 2 minutes.-   4) Glycerin and remaining half of the maltitol syrup was added and    mixing continued for about 1.5 minutes.-   5) Remaining xylitol was gradually added and mixing continued for    approximately 2 minutes.-   6) Flavor was added and mixing continued for 2-3 minutes until batch    was uniform. Upon cooling, rectangular pieces, 2.0-2.2g/piece, were    extruded.

Subjects chosen for the study had appreciably stained teeth (Vita ShadeGuide, Omsk., values >7, i.e., “darker” than “B4”) and had not hadteeth-whitening procedure performed for at least 3 years prior. Theresults, shown below in Table 3, conclusively showed that that six ofthe thirty two combinations demonstrated appreciable teeth-whitening.

TABLE 3 Teeth-whitening obtained using various carbamide peroxidebicarbonate gum compositions Peroxide containing gum % BC B C E F H I KL 5 0-1 0-1 0-1   0-1     1-1.5   1-1.5 1.5-2   1.5-2   10 0-1 0-1 0-1  0-1   1.5-2   1.5-2     2-2.5   2-2.5 15 0-1 0-1 1-1.5 1-1.5 3.5-5  2.5-3     3-3.5   3-3.5 0 0-1 0-1 0-1   0-1   0.5-1     1-1.5 1.0-1.51.0-1.5 % BC: % sodium bicarbonate in the bicarbonate containing gum

Compositions made with 15% sodium bicarbonate containing gum performedthe best. More specifically, the best combination for teeth-whiteningcommercial product was found to be the combination of carbamide peroxidegum composition “H” with 15% bicarbonate containing gum composition asits complement. Without being limited by any theory or mechanism ofaction, it is believed that the most likely reason the “peroxide” gumcomposition “I” did not perform as well as the composition “H” is thatwith 5 % citric acid, “I” has excess citric acid that reacts with thebicarbonate ion to reduce the effective amount of bicarbonate, leadingto the pH of the oral cavity not being the most favorable to activatethe peroxide moiety in-situ. See Table 1. Note that the composition “H”has 2% citric acid.

Also, some of the test subjects experienced slight discomfort when usingthe peroxide gum tablets having 15% carbamide peroxide (K, L), whereasno sensitivity was reported with the use of the 10% peroxide gums (H, I)when employed with its 15% bicarbonate gum complement. Notably, it wasgenerally observed that the higher the amount of sodium bicarbonate withrespect to the amount of carbamide peroxide, the lower was the observedtooth sensitivity.

Example 5. Two-Gum (Biphasic) Composition made by Extrusion

The compositions of the peroxide gum and the bicarbonate gum of anexemplary two-gum (biphasic) composition is shown below.

Peroxide Gum

Ingredient Amount Carbamide peroxide 200 mg Gum base 660 mg Xylitol 900Spearmint oil (spray-dried) 100 mg Glycerin  40 mg Citric Acid  50 mgSucralose  15 mg Amorphous silica  50 mg

Procedure

-   1) Gum base and xylitol were added to a warm mixer and mixing    started.-   2) Upon softening of the resulting mixture, about half of the    remaining xylitol was added and mixing continued for 2 minutes.-   3) Citric acid, silicon dioxide, and carbamide peroxide were added    and mixing continued for approximately 2 minutes.-   4) Glycerin and coolant were added and mixing continued for    approximately 1.5 minutes.-   5) Remaining xylitol was gradually added and mixing continued for    approximately 2 minutes.-   6) Sucralose was added and mixed for approximately 1 minute.-   7) SD flavor was added and mixing continued for 2-3 minutes until    batch was uniform. Upon cooling, rectangular pieces, 2.0-2.2g/piece,    were extruded.

Bicarbonate Gum

Ingredient Amount Sodium bicarbonate 300 mg Amorphous silica  30 mg Gumbase (“Nova-T/PIB-T”) 650 mg Spray dried peppermint oil 100 mg Glycerin 60 mg Xylitol 890 mg Surfactant (SLS)  5 mg Calcium carbonate  5 mgSodium carbonate  5 mg Sucralose  60 mg Titanium Dioxide  5 mg Lecithin 3 mg

Procedure

-   1) Gum base, xylitol, and titanium dioxide were added to a warm    mixer and mixing started.-   2) Upon softening of the resulting mixture, about half of the    remaining xylitol was added and mixing continued for 2 minutes.-   3) Coolant, sucralose, and sodium bicarbonate/silicon dioxide were    added to the mixture and mixing continued for approximately 2    minutes.-   4) Glycerin was added and mixing continued for approximately 1.5    minutes.-   5) Remaining xylitol was gradually added and mixing continued for    approximately 2 minutes.-   6) Flavor was added and mixing continued for 2-3 minutes until batch    was uniform. Upon cooling, rectangular pieces, 2.0-2.2g/piece, were    extruded.

Example 6. Demonstration of Synergistic Teeth-Whitening Activity withSimultaneous use of the Peroxide Gum and the Bicarbonate Gum

Improvement in teeth-whitening by biphsic gum (combination of peroxidegum and bicarbonate gum) was compared to the improvement inteeth-whitening achieved with the peroxide gun and the bicarbonate gumalone.

Twelve subjects were chosen, none ever having had their teeth bleached.Their teeth were heavily stained due to smoking. Subjects qualified forthe study if they demonstrated whitening levels darker than “B4” gradeusing the Vita Shade Guide (Classic). The subjects used: (a) either asingle peroxide gum prepared according to Example 4 (ca. 2 gram perpiece), or; (b) a single bicarbonate gum prepared according to Example 4(2 gram per piece), or; (c) the two gums together, chewedsimultaneously. The gums were chewed for 30 minutes. The results of thechewing are shown in Table 4 below.

TABLE 4 Teeth-whitening efficacy of peroxide and bicarbonate gumcombined compared to that of peroxide gum or bicarbonate gum Type of GumPeroxide Bicarbonate Peroxide Gum + Subject Gum Gum Bicarbonate Gum 1 00 3 2 0 0 2 3 1 0 4 4 0 0 4 5 1 0 5 6 0 0 2 7 0 0 3 8 1 0 4 9 1 1 4 10 10 3 11 1 1 5 12 1 1 4 Average 0.58 0.25 3.58 shade change in whitening

The results show a dramatic increase in whitening observed for theperoxide guru due to the presence of the bicarbonate gum. A tenfoldincrease in whitening (1000% increase) was observed. Specifically,average whitening levels were observed to be very little (0.58 shade) ifany, when the subject only used the “peroxide gum” (no “bicarbonateguru”). Likewise, when the subjects chewed only the “bicarbonate gum,”no appreciable teeth-whitening took place. In stark contrast, when thetwo gums were chewed together, a shade change of between 2-5 shades wasobserved, with an average change of about 3.6 shades.

These data demonstrate a strong whitening effect when both gums arechewed together. The magnitude of the effect is much greater than wouldbe expected from a teeth-whitener in general, and especially from ateeth-whitening gum. The effect is a result of sodium bicarbonate andcarbamide peroxide being present together in an oral mixture. Further,the magnitude of the teeth-whitening effect is much greater than wouldbe expected if sodium bicarbonate functioned solely by activating theperoxide by pH control.

Example 7. Single Composition Multi-Phasic Teeth Whitening Tablet

The three compositions below were compounded using a standard ribbonblender at low speed and pressed into a single multi-layered tablet,having the middle layer (of the three-layer tablet) as the barrier layercomprising anhydrous chewing gum base and no active.

Bicarbonate Layer (Phase)

Ingredient Amount Sodium Bicarbonate 375 mg Amorphous Silica  20 mg Gumbase 800 mg Spray dried peppermint oil 100 mg Xylitol 700 mg Calciumcarbonate  5 mg Sodium carbonate  5 mg Magnesium Stearate  80 mg StearicAcid 125 mg Microcrystalline Cellulose 200 mg Coating (xylitol)  25 mg

Peroxide Layer (Phase)

Ingredient Amount Carbamide peroxide 250 mg Gum base 900 mg Xylitol 850mg Sorbitol 500 mg Peppermint oil (spray-dried)  25 mg Sucralose  30 mgCitric Acid  50 mg Magnesium Stearate  75 mg Stearic Acid 100 mgMicrocrystalline Cellulose 125 mg

Intermediary Barrier Layer (Phase)

Ingredient Amount Amorphous silica  20 mg Gum base 800 mg Spray driedpeppermint oil 100 mg Xylitol 800 mg Sorbitol 225 mg Magnesium Stearate 80 mg Stearic Acid 155 mg Microcrystalline Cellulose 300 mg

Example 8, Evidence of Chemotherapeutic Effect with Simultaneous use ofthe Peroxide Gum and the Bicarbonate Gum

All of the test subjects of Example 6 described a lessening ofsensitivity to peroxide when the bicarbonate gums having greater than10% sodium bicarbonate were chewed together with the peroxide gums. Thiseffect was especially noticeable for the peroxide gums comprising 15%carbamide peroxide. In these gums sodium bicarbonate was present between250 mg and 400 mg and carbamide peroxide was present between 175 mg and400 mg. Condition of the gums and breath were observed to have improved,especially for those cases where the patients had inflamed gums atbaseline (symptoms typical for gingivitis). The counts of anaerobic andaerobic bacteria decreased dramatically, even after only one 30-minutetreatment. These results strongly suggest that the two-composition oraltreatment helps remediate symptoms of periodontal diseases, and oralmalodor, not only by removing stains and debris from the teeth surface,but also by affecting positive change to the micro-flora inherent to thehuman oral cavity.

1-51. (canceled)
 52. A method for whitening teeth in a human subject inneed thereof, the method comprising: placing in the oral cavity of thesubject a first composition and a second composition; and chewingtogether the first and second composition; wherein the first compositionis a chewable composition comprising, an anhydrous chewing gum basehaving water content of about 1% or less, an anhydrous fruit acid,carbamide peroxide having water content of about 2% or less, and one ormore gum additives, wherein the ratio of gum base: carbamide peroxide:fruit acid, in percent weight relative to the composition, is about10-50:1-20:0.5-8, and the one or more gum additives are present in anamount sufficient to reach 100% of the weight of the composition; andthe second composition is a chewable composition comprising a source ofbicarbonate ion, a gum base, and one or more gum additives, wherein thesource of bicarbonate ion and the gum base are present, respectively, ina ratio of about 5-30:15-50 in percent weight relative to the secondcomposition, and the one or more gum additives are present at an amountnecessary to reach 100% of the weight of the second region, and whereinthe total weight of the first and the second composition is about 1 g toabout 10 g and the chewing provides about 20 mg to about 400 mg hydrogenperoxide equivalents.
 53. The method of claim 52, wherein the source ofbicarbonate ion is sodium bicarbonate.
 54. The method of claim 53,wherein in the first and the second chewable composition combined, theratio of fruit acid: carbamide peroxide: sodium bicarbonate, by mass isabout 0.5-5:5-20:10-35.
 55. The method of claim 52, wherein the secondcomposition further comprises a metal carbonate at about 0.001-1% of theweight of the second composition.
 56. The method of claim 52, whereinthe fruit acid is citric acid.
 57. The method of claim 53, wherein,sodium bicarbonate is present at three times or more the amount of thefruit acid.
 58. The method of claim 52, wherein pH of the saliva of thehuman during chewing is about 5.5 to about
 7. 59. The method of claim52, wherein the composition is chewed for 1 to 30 minutes during thechewing step.